JAMA Netw Open. 2026 Jun 1;9(6):e2619362. doi: 10.1001/jamanetworkopen.2026.19362.
ABSTRACT
IMPORTANCE: Among individuals who meet the diagnostic threshold for type 2 diabetes (T2D), timely initiation of antidiabetic medication (ADM) is essential for lowering long-term cardiovascular risk.
OBJECTIVE: To estimate the association between ADM initiation timing-specifically within 3, 6, or 12 months-and the risk of major adverse cardiovascular events (MACE) and all-cause mortality among individuals newly meeting diagnostic criteria for T2D.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study used target trial emulation to analyze health screening data linked to health insurance claims in Korea (2013-2022) using a clone-censor-weight approach. Participants were adults with newly detected glycated hemoglobin (HbA1c) of 6.5% or greater or fasting plasma glucose of 126 mg/dL or greater. Data analysis was conducted from January to August 2025.
EXPOSURES: Eligible participants were cloned into 4 treatment strategies: ADM initiation within 3, 6, or 12 months or no initiation within 12 months (strategy 1, 2, 3, and control, respectively).
MAIN OUTCOMES AND MEASURES: Five-year absolute risk difference (RD) and risk ratio (RR) of 3-point MACE (stroke, myocardial infarction, and all-cause mortality) and all-cause mortality were estimated using Kaplan-Meier survival probabilities along with 95% CIs from 1000-sample nonparametric bootstrapping.
RESULTS: A total of 23 452 eligible participants (mean [SD] age, 48.2 [11.1] years; 5790 [24.7%] female; mean [SD] HbA1c, 6.9% [1.1%]) were cloned into 4 treatment strategies. Earlier ADM initiation compared with the control showed progressively lower point estimates for 3-point MACE (RR, 0.32; 95% CI, 0.15 to 1.11 for strategy 1; RR, 0.65; 95% CI, 0.41 to 1.29 for strategy 2; RR, 0.93; 95% CI, 0.70 to 1.41 for strategy 3), though it did not achieve statistical significance. Corresponding RDs were -0.97% (95% CI, -1.26% to 0.14%), -0.49% (-0.84% to 0.40%), and -0.10% (-0.44% to 0.57%), respectively. ADM initiation within 3 months yielded significant risk reduction for all-cause mortality compared with the control in both relative (RR, 0.31; 95% CI, 0.10-0.98) and absolute (RD, -0.40%; 95% CI, -0.57% to -0.01%) scales.
CONCLUSIONS AND RELEVANCE: In this cohort study, earlier ADM initiation following the diagnostic threshold for T2D showed a lower risk of mortality, suggesting a potential cardiovascular benefit of early glycemic control; however, given the low event counts and the observational nature of the study, further evaluation in larger studies is warranted before definitive conclusions can be drawn.
PMID:42329653 | DOI:10.1001/jamanetworkopen.2026.19362
